Plasma Exosomal miRNA Expression Profile as Oxaliplatin-Based Chemoresistant Biomarkers in Colorectal Adenocarcinoma.
Plasma Exosomal miRNA Expression Profile as Oxaliplatin-Based Chemoresistant Biomarkers in Colorectal Adenocarcinoma.
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血浆外泌体 miRNA 表达谱作为结直肠腺癌中奥沙利铂耐药生物标志物
DOI：
10.3389/fonc.2020.01495
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发表时间：
2020
影响因子：
4.7
通讯作者：
Ba Y
中科院分区：
文献类型：
--
作者：
Han J;Sun W;Liu R;Zhou Z;Zhang H;Chen X;Ba Y
背景：化疗是结直肠癌最常用的治疗方法之一，但化疗耐药的发生是不可避免的。获得化学抗性的即时和准确的诊断是具有挑战性的。在本研究中，研究了循环外泌体miRNA作为CRC患者中基于奥沙利铂的化学耐药生物标志物的潜力。研究方法：通过miRNA微阵列分析来分析敏感和耐药患者中的血浆外泌体miRNA，然后在两个独立的队列中用定量逆转录聚合酶链反应（RT-qPCR）测定进行验证。采用ROC曲线分析判断诊断准确性。同时进行Logistic回归分析和斯皮尔曼等级相关检验。最后，利用生物信息学方法对筛选出的miRNAs在化疗耐药中的潜在分子机制进行了初步探讨。结果如下：与化疗敏感患者相比，miRNA微阵列分析在化疗耐药患者中鉴定出4种上调的miRNA和20种下调的miRNA。选择12种显著失调的miRNA进行进一步研究，其中6种（miR-100、miR-92 a、miR-16、miR-30 e、miR-144- 5 p和let-7i）被证实是显著且一致失调的（>1.5倍，P < 0.05）。六种miRNA的组合具有最高的AUC（0.825，95%CI，0.753-0.897）。这6种miRNAs的表达水平与肿瘤部位、分期及化疗方案无关。只有miR-100在低组织学分级中显著上调。GO分析和KEGG通路分析表明，miRNAs与RNA聚合酶II的转录相关，并在PI 3 K-AKT信号通路、AMPK信号通路和FoxO信号通路中富集。结论：我们鉴定了一组血浆外泌体miRNA，其包含miR-100、miR-92 a、miR-16、miR-30 e、miR-144- 5 p和let-7i，其可以显著区分化学抗性患者和化学敏感患者。循环外泌体miRNA的检测可以作为监测CRC患者对化疗反应的有效方法。靶向这些miRNA也可能是CRC治疗的一种有希望的策略。
Background: Chemotherapy is one of the most common therapies used in the treatment of colorectal cancer (CRC), but chemoresistance inevitably occurs. It is challenging to obtain an immediate and accurate diagnosis of chemoresistance. The potential of circulating exosomal miRNAs as oxaliplatin-based chemoresistant biomarkers in CRC patients was investigated in this study. Methods: Plasma exosomal miRNAs in sensitive and resistant patients were analyzed by miRNA microarray analysis, followed by verification with a quantitative reverse-transcription polymerase chain reaction (RT-qPCR) assay in two independent cohorts. The diagnostic accuracy was determined by ROC curve analysis. Logistic regression analysis and Spearman's rank correlation test were also performed. Finally, bioinformatics was used to preliminarily explore the potential molecular mechanism of the selected miRNAs in chemoresistance. Results: miRNA microarray analysis identified four upregulated miRNAs and 20 downregulated miRNAs in chemoresistant patients compared to chemosensitive patients. Twelve markedly dysregulated miRNAs were selected for further investigation, of which six (miR-100, miR-92a, miR-16, miR-30e, miR-144-5p, and let-7i) were verified to be significantly and consistently dysregulated (>1.5-fold, P < 0.05). The combination of the six miRNAs had the highest AUC (0.825, 95% CI, 0.753–0.897). The expression level of these 6 miRNAs was not correlated with tumor location, stage, or chemotherapy program. Only miR-100 was significantly upregulated in low histological grade. GO analysis and KEGG pathway analysis showed that miRNAs were related to RNA polymerase II transcription and enriched in the PI3K-AKT signaling pathway, AMPK signaling pathway, and FoxO signaling pathway. Conclusions: We identified a panel of plasma exosomal miRNAs, containing miR-100, miR-92a, miR-16, miR-30e, miR-144-5p, and let-7i, that could significantly distinguish chemoresistant patients from chemosensitive patients. The detection of circulating exosomal miRNAs may serve as an effective way to monitor CRC patient responses to chemotherapy. Targeting these miRNAs may also be a promising strategy for CRC treatment.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
血清 miRNA 表达谱作为 II/III 期结直肠腺癌的预后生物标志物
影响因子：
4.6
作者：
Li J;Liu Y;Wang C;Deng T;Liang H;Wang Y;Huang D;Fan Q;Wang X;Ning T;Liu R;Zhang CY;Zen K;Chen X;Ba Y
通讯作者：
Ba Y
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Ning ZQ;Lu HL;Chen C;Wang L;Cai W;Li Y;Cao TH;Zhu J;Shu YQ;Shen H
通讯作者：
Shen H
影响因子：
11.5
作者：
Jin, Xiance;Chen, Yanfan;Xie, Congying
通讯作者：
Xie, Congying
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影响因子：
11.1
作者：
Chen, Tingting;Wang, Cheng;Zhang, Chunni
通讯作者：
Zhang, Chunni